Positive Phase 3 Study of ORKAMBI® in Children With Cystic Fibrosis Ages 6-11 Who Have Two Copies of the F508del Mutation Supports a Submission to the European Medicines Agency in the First Half of 2017

- ORKAMBI was well tolerated with safety data that were similar to
data from previous Phase 3 open-label safety study -

- Approximately 3,400 children ages 6-11 have two copies of the
F508del mutation in Europe -

BOSTON--(BUSINESS WIRE)--
Vertex
Pharmaceuticals Incorporated (Nasdaq:VRTX) today announced the
results of a Phase 3 study of ORKAMBI® (lumacaftor/ivacaftor)
in children with cystic fibrosis (CF) ages 6 through 11 who have two
copies of the F508del mutation. The study met its primary
endpoint of absolute change in lung clearance index (LCI2.5)
through 24 weeks of treatment, demonstrating a statistically significant
improvement in LCI2.5 among patients treated with ORKAMBI
compared to placebo. LCI is a sensitive measure of lung function in
early CF disease and the European Medicines Agency (EMA) agreed to the
primary endpoint for this study. In the first half of 2017, Vertex plans
to submit a Marketing Authorization Application (MAA) line extension to
the EMA for the use of ORKAMBI in this patient population. Data from a
previous Phase 3 open-label safety study in children ages 6 through 11
supported the U.S. Food and Drug Administration approval of ORKAMBI in
September 2016. In this second study, ORKAMBI was well tolerated with
safety data that were similar to data from the previous Phase 3 study.
There are approximately 3,400 children ages 6 through 11 who have two
copies of the F508del mutation in Europe.

"This study is an important complement to recently presented long-term
data in patients 12 years and older suggesting ORKAMBI may modify the
course of CF. These new data demonstrate that treating the underlying
cause of the disease with ORKAMBI improves lung function in even younger
patients," said Jeffrey Chodakewitz, M.D., Executive Vice President and
Chief Medical Officer at Vertex. "We are preparing to submit these
important data to the EMA in the first half of 2017, and we look forward
to bringing ORKAMBI to eligible children in Europe as soon as possible."

"CF is a progressive disease that begins at birth, and traditional
measurements do not always detect the early lung damage that occurs in
children," said Felix Ratjen, M.D., Division Chief of Pediatric
Respiratory Medicine at The Hospital for Sick Children Toronto,
Professor of Pediatrics at The University of Toronto, a Senior Scientist
at the Research Institute in the Department of Physiology and
Experimental Medicine, and Principal Investigator for the study. "LCI is
a sensitive measure of lung function, and these new data demonstrate
that treating children early with ORKAMBI can improve lung function."

Summary of Key Data

The data announced today are from a Phase 3, randomized, double-blind,
placebo-controlled, parallel-group, multicenter study to evaluate the
efficacy and safety of ORKAMBI in children ages 6 through 11 who have
two copies of the F508del mutation. The study compared children
who received treatment with lumacaftor (200 mg q12h) in combination with
ivacaftor (250 mg q12h) (n=103) with those who received placebo (n=101)
for 24 weeks. Baseline lung function as measured by percent predicted
forced expiratory volume in one second (ppFEV1) was 89.8.

The primary endpoint of the study was absolute change in lung clearance
index (LCI2.5) from baseline through Week 24. LCI2.5
measures the efficiency of ventilation in the lungs by quantifying how
long it takes to reduce an inhaled tracer gas to 2.5 percent of its
starting value. LCI is considered a more sensitive measure to detect
early lung disease than forced expiratory volume in one second (FEV1).
Higher LCI scores indicate poorer lung function. To participate in the
study, children had to have an LCI2.5 ≥7.5 at the initial
screening visit, considered the cutoff for abnormal gas exchange. At
baseline, mean LCI2.5 was 10.28. In the study, children
treated with ORKAMBI experienced an improvement in lung function (LCI2.5)
of -1.09 compared to placebo through 24 weeks (p < 0.0001).

Improvements in secondary endpoints were also observed in this study,
including a statistically significant reduction in sweat chloride
assessed by the average absolute change from baseline at Day 15 and Week
4 (-20.8 mmol/L compared to placebo; p < 0.0001). Improvements in body
mass index (BMI) and the Cystic Fibrosis Questionnaire-Revised (CFQ-R)
respiratory domain score were also observed, although not statistically
significant. The improvement in absolute change from baseline in body
mass index (BMI) at Week 24 was 0.11 kg/m2 compared to
placebo (p=0.2522) and the improvement in absolute change from baseline
in CFQ-R respiratory domain score through Week 24 was 2.5 points
compared to placebo (p=0.0628). Lung function as assessed by an absolute
change from baseline in ppFEV1 through Week 24 was an
additional endpoint of the study for which a statistically significant
improvement of 2.4 percentage points compared to placebo (p=0.0182) was
observed.

Overall, safety data were similar to those observed in a previous Phase
3 open-label safety study in children ages 6 through 11. In this study,
the most common adverse events that occurred more frequently among those
receiving ORKAMBI compared to placebo were infective pulmonary
exacerbation, productive cough, nasal congestion, oropharyngeal pain,
abdominal pain upper, headache, upper respiratory tract infection and
sputum increased. The incidence of liver enzyme elevations and
respiratory events were slightly higher in the ORKAMBI group compared to
placebo. Treatment discontinuations due to adverse events were low
across those receiving placebo (n=2) and those receiving ORKAMBI (n=3)
through 24 weeks.

INDICATION AND IMPORTANT SAFETY INFORMATION FOR ORKAMBI® (lumacaftor/ivacaftor)
TABLETS

ORKAMBI is a prescription medicine used for the treatment of cystic
fibrosis (CF) in patients age 6 years and older who have two copies of
the F508del mutation (F508del/F508del) in their CFTR gene.
ORKAMBI should only be used in these patients. It is not known if
ORKAMBI is safe and effective in children under 6 years of age.

Patients should not take ORKAMBI if they are taking certain medicines
or herbal supplements, such as: the antibiotics rifampin or
rifabutin; the seizure medicines phenobarbital, carbamazepine, or
phenytoin; the sedatives/anti-anxiety medicines triazolam or midazolam;
the immunosuppressant medicines everolimus, sirolimus, or tacrolimus; or
St. John's wort.

Before taking ORKAMBI, patients should tell their doctor if they: have
or have had liver problems; have kidney problems; have had an organ
transplant; are using birth control (hormonal contraceptives, including
oral, injectable, transdermal or implantable forms). Hormonal
contraceptives should not be used as a method of birth control when
taking ORKAMBI. Patients should tell their doctor if they are pregnant
or plan to become pregnant (it is unknown if ORKAMBI will harm the
unborn baby) or if they are breastfeeding or planning to breastfeed (it
is unknown if ORKAMBI passes into breast milk).

ORKAMBI may affect the way other medicines work and other medicines may
affect how ORKAMBI works. Therefore, the dose of ORKAMBI or other
medicines may need to be adjusted when taken together. Patients should
especially tell their doctor if they take: antifungal medicines such as
ketoconazole, itraconazole, posaconazole, or voriconazole; or
antibiotics such as telithromycin, clarithromycin, or erythromycin.

When taking ORKAMBI, patients should tell their doctor if they
stop ORKAMBI for more than 1 week as the doctor may need to change the
dose of ORKAMBI or other medicines the patient is taking. It is unknown
if ORKAMBI causes dizziness. Patients should not drive a car, use
machinery, or do anything requiring alertness until the patient knows
how ORKAMBI affects them.

ORKAMBI can cause serious side effects including:

High liver enzymes in the blood, which can be a sign of liver injury,
have been reported in patients receiving ORKAMBI. The patient's
doctor will do blood tests to check their liver before they start
ORKAMBI, every three months during the first year of taking ORKAMBI, and
annually thereafter. The patient should call the doctor right away if
they have any of the following symptoms of liver problems: pain or
discomfort in the upper right stomach (abdominal) area; yellowing of the
skin or the white part of the eyes; loss of appetite; nausea or
vomiting; dark, amber-colored urine; or confusion.

Respiratory events such as shortness of breath or chest tightness
were observed in patients when starting ORKAMBI. If a patient has
poor lung function, their doctor may monitor them more closely when
starting ORKAMBI.

An increase in blood pressure has been seen in some patients treated
with ORKAMBI. The patient's doctor should monitor their blood
pressure during treatment with ORKAMBI.

Abnormality of the eye lens (cataract) has been noted in some
children and adolescents receiving ORKAMBI and ivacaftor, a component of
ORKAMBI. For children and adolescents, the patient's doctor should
perform eye examinations prior to and during treatment with ORKAMBI to
look for cataracts.

Please click here
to see the full Prescribing Information for ORKAMBI.

About Cystic Fibrosis

Cystic fibrosis is a rare, life-threatening genetic disease affecting
approximately 75,000 people in North America, Europe and Australia.

CF is caused by a defective or missing CFTR protein resulting from
mutations in the CFTR gene. Children must inherit two
defective CFTR genes — one from each parent — to have
CF. There are approximately 2,000 known mutations in the CFTR gene.
Some of these mutations, which can be determined by a genetic test, lead
to CF by creating defective or too few CFTR proteins at the cell
surface. The defective or missing CFTR protein results in poor flow of
salt and water into or out of the cell in a number of organs, including
the lungs. This leads to the buildup of abnormally thick, sticky mucus
that can cause chronic lung infections and progressive lung damage in
many patients that eventually leads to death. The median predicted age
of survival for a person born today with CF is 41 years, but the median
age of death is 27 years.

About Vertex

Vertex is a global biotechnology company that aims to discover, develop
and commercialize innovative medicines so people with serious diseases
can lead better lives. In addition to our clinical development programs
focused on cystic fibrosis, Vertex has more than a dozen ongoing
research programs aimed at other serious and life-threatening diseases.

Founded in 1989 in Cambridge, Mass., Vertex today has research and
development sites and commercial offices in the United
States, Europe, Canada and Australia. For seven years in a row, Science magazine
has named Vertex one of its Top Employers in the life sciences. For
additional information and the latest updates from the company, please
visit www.vrtx.com.

Vertex initiated its CF research program in 2000 as part of a
collaboration with CFFT, the nonprofit drug discovery and development
affiliate of the Cystic Fibrosis Foundation. KALYDECO®
(ivacaftor) and ORKAMBI (lumacaftor/ivacaftor) were discovered by Vertex
as part of this collaboration.

Special Note Regarding Forward-looking Statements

This press release contains forward-looking statements as defined in the
Private Securities Litigation Reform Act of 1995, including, without
limitation, the statements from Dr. Chodakewitz and Dr. Ratjen and
statements regarding Vertex's plans to submit a Marketing Authorization
Application line extension to the EMA. While Vertex believes the
forward-looking statements contained in this press release are accurate,
these forward-looking statements represent the company's beliefs only as
of the date of this press release and there are a number of factors that
could cause actual events or results to differ materially from those
indicated by such forward-looking statements. Those risks and
uncertainties include, among other things, that data from the company's
development programs may not support registration or further development
of ORKAMBI or its other compounds due to safety, efficacy or other
reasons, and other risks listed under Risk Factors in Vertex's annual
report and quarterly reports filed with the Securities and Exchange
Commission and available through the company's website at www.vrtx.com.
Vertex disclaims any obligation to update the information contained in
this press release as new information becomes available.